On May 1, 2025 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, reported financial results for the first quarter ended March 31, 2025, and provided a corporate update (Press release, Arvinas, MAY 1, 2025, View Source [SID1234652423]).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
"The positive readout from our first Phase 3 trial, the first ever for a PROTAC, is a tremendous accomplishment and one which we are very proud of," said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. "Our conviction is high that vepdegestrant can be highly competitive as a monotherapy treatment option for metastatic breast cancer in the second-line, ESR1 mutant setting. We are on track to submit a regulatory filing with health authorities, which we believe could result in the first ever approval of a PROTAC and an exciting opportunity to bring a novel treatment to patients with ESR1 mutant advanced metastatic breast cancer."
"Beyond the second-line monotherapy opportunity, we and our partners at Pfizer have removed plans for a Phase 3 first-line combination trial with atirmociclib, as well as the planned Phase 3 second-line combination trial with a CDK4/6 inhibitor, from our joint development plan," continued Dr. Houston. "This decision was made following a review of the totality of emerging information, including external data results, the evolving treatment landscape in metastatic breast cancer, and long-term capital allocation. We and Pfizer are working to evaluate future combination plans with the potential to maximize patient benefit and shareholder value."
1Q 2025 Business Highlights and Recent Developments
Vepdegestrant: Oral PROTAC ER degrader: As part of Arvinas global collaboration with Pfizer, the companies:
Reported positive topline data for VERITAC-2, the Phase 3 pivotal 2L+ trial of monotherapy vepdegestrant in patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer, in the estrogen receptor 1-mutant population.
VERITAC-2 data accepted for oral presentation at the 2025 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (May 30 – June 3, 2025).
Announced that Pfizer will add a vepdegestrant/KAT6 cohort to its ongoing Phase 1 trial evaluating its investigational KAT6 inhibitor (PF-07248144) in combination with endocrine therapies following CDK4/6 inhibitor treatment.
Removed the first-line Phase 3 combination trial with Pfizer’s novel investigational CDK4 inhibitor, atirmociclib, from the agreed-upon joint development plan.
Removed the second-line Phase 3 combination trial with a CDK4/6 inhibitor from the agreed-upon joint development plan.
ARV-102: Oral PROTAC LRRK2 degrader
Presented single ascending dose (SAD) and multiple ascending dose (MAD) data from the ongoing Phase 1 clinical trial in healthy volunteers in an oral session at the Alzheimer’s Disease/Parkinson’s Disease (AD/PD) conference in Vienna, Austria demonstrating blood-brain barrier penetration, and central and peripheral LRRK2 degradation:
At a single oral dose of at least 60 mg, and once daily repeated oral doses of at least 20 mg, ARV-102 achieved greater than 50% LRRK2 reduction in the cerebral spinal fluid (CSF) and greater than 90% LRRK2 reduction in the peripheral blood mononuclear cells (PBMCs), indicating substantial central and peripheral LRRK2 protein degradation.
Inhibition of Rab10 phosphorylation in PBMCs and reduction of bis(monoacylglycerol)phosphate (BMP) in urine following single doses of ARV-102, signifying downstream LRRK2 pathway engagement.
Bioavailable and brain penetrant with dose dependent exposure in the CSF.
ARV-102 was generally safe and well tolerated with no serious adverse events reported after single or multiple doses.
ARV-393: Oral PROTAC BCL6 degrader
Continued recruiting patients in the first-in-human Phase 1 clinical trial in patients with non-Hodgkin lymphoma (NHL) (ClinicalTrials.gov Identifier: NCT06393738).
Presented new preclinical data of ARV-393 in combination with standard of care (SOC) biologic agents and small molecule inhibitors (SMI) in high-grade B-cell lymphoma (HGBCL) and aggressive diffuse large B-cell lymphoma (DLBCL) models at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that ARV-393 had broad and significant combinability with:
SOC chemotherapy:
ARV-393 in combination with R-CHOP, induced significantly greater tumor growth inhibition (TGI) compared with rituximab, CHOP, R-CHOP, or ARV-393 alone, with complete tumor regressions enabled by the combination.
SOC biologics:
Similarly, the combination of ARV-393 and SOC biologics targeting CD19 (tafasitamab), CD79b (polatuzumab vedotin), or CD20 (rituximab) resulted in tumor regressions and demonstrated significantly stronger TGI compared with either agent alone.
Investigational small molecule inhibitors targeting clinically validated oncogenic drivers of lymphoma:
Combination of ARV-393 with a BTK inhibitor (acalabrutinib), a BCL2 inhibitor (venetoclax), or an EZH2 inhibitor (tazemetostat) induced tumor regressions in the majority of mice.
Overall, current preclinical data suggest that ARV-393 has the potential to be an attractive combination partner for development of novel therapies for lymphoma, including chemo-free combination regimens and/or "all oral" treatment options.
ARV-806: Novel PROTAC KRAS G12D degrader
Filed an Investigational New Drug (IND) application and received a safe-to-proceed letter from the U.S. Food and Drug Administration.
Corporate updates:
As part of a Company-wide cost reduction effort:
Announced the removal of two Phase 3 trials from the vepdegestrant development plan
Announced a reduction in workforce of approximately one-third across the Company to streamline operations across the organization and enable the efficient progression of the Company’s portfolio. The reduction is planned to be completed in the second quarter of 2025.
Announced a reprioritization of the Company’s preclinical portfolio to focus on assets that have the greatest potential to deliver value for patients, physicians and shareholders.
Updated guidance for its cash runway into the second half of 2028.
"We continuously evaluate and refine our long-term strategy, and recent challenges in the capital markets have required us to expeditiously evaluate our business priorities and capital needs," continued Dr. Houston. "Although difficult, the workforce reduction is a prudent decision that we believe will right-size the Company for future success. I want to thank all the talented employees who were directly impacted by this decision. I’m proud of the progress we have made together, and want to acknowledge their contributions, and commitment, to discovering and developing new treatment options for patients with serious diseases."
Anticipated Upcoming Milestones and Expectations
Vepdegestrant: Oral PROTAC ER degrader
As part of Arvinas’ global collaboration with Pfizer, the companies plan to:
Present detailed results from the VERITAC-2 Phase 3 clinical trial in a late-breaker oral presentation at ASCO (Free ASCO Whitepaper) (2Q 2025).
VERITAC-2 abstract will be featured in the ASCO (Free ASCO Whitepaper) press program and has been selected to be included in the "2025 Best of ASCO (Free ASCO Whitepaper) Program."
Share data with global regulatory authorities to potentially support regulatory filings (2Q 2025) and submit new drug application to the U.S. Food and Drug Administration for potential approval (2H 2025).
Add a combination cohort of vepdegestrant plus Pfizer’s KAT6 inhibitor (PF-07248144) to Pfizer’s ongoing Phase 1 trial (NCT04606446).
The trial is currently evaluating Pfizer’s KAT6 inhibitor in combination with endocrine therapies following CDK4/6 inhibitor treatments; the trial is being operationalized and funded by Pfizer.
ARV-102: Oral PROTAC LRRK2 degrader
Present final data from the SAD/MAD cohorts of the Phase 1 clinical trial in healthy volunteers (2H 2025).
Continue enrollment and present initial data from the SAD cohort of the ongoing Phase 1 clinical trial in patients with Parkinson’s disease (2H 2025).
Initiate the MAD cohort of the Phase 1 clinical trial in patients with Parkinson’s disease (2H 2025).
ARV-393: Oral PROTAC BCL6 degrader
Present new preclinical data demonstrating single agent activity of ARV-393 in patient derived xenograft models of transformed Follicular Lymphoma and a patient-derived xenograft model of nTFHL-AI (angioimmunoblastic type of nodal T-follicular helper cell lymphoma), a rare and aggressive non-Hodgkin lymphoma with high unmet need and limited treatment options, at the European Hematology Association (EHA) (Free EHA Whitepaper) 2025 conference in Milan, Italy (June 12-15, 2025).
Share preclinical data in combination with an emerging SOC option in 2L DLBCL (2H 2025).
Share preliminary clinical data from the ongoing Phase 1 clinical trial in patients with NHL (NCT06393738) (2H 2025).
ARV-806: Novel PROTAC KRAS G12D degrader
Initiate a first-in-human Phase 1 trial in patients with solid tumors harboring KRAS G12D mutations (2H 2025).
Financial Guidance
Based on its current operating plan, Arvinas believes its cash, cash equivalents, and marketable securities as of March 31, 2025, is sufficient to fund planned operating expenses and capital expenditure requirements into the second half of 2028.
First Quarter Financial Results
Cash, Cash Equivalents, and Marketable Securities Position: As of March 31, 2025, cash, cash equivalents and marketable securities were $954.3 million as compared with cash, cash equivalents and marketable securities of $1,039.4 million as of December 31, 2024. The decrease in cash, cash equivalents and marketable securities of $85.1 million for the three months ended March 31, 2025 was primarily related to cash used in operations of $85.1 million, the purchase of lab equipment and leasehold improvements of $0.4 million and $0.1 million of long term debt repayments, partially offset by unrealized gains on marketable securities of $0.5 million.
Research and Development Expenses: Generally Accepted Accounting Principles (GAAP) Research and development (R&D) expenses were $90.8 million for the quarter ended March 31, 2025, as compared with $84.3 million for the quarter ended March 31, 2024. The increase in research and development expenses of $6.5 million for the quarter was primarily due to an increase in external expenses of $7.8 million, partially offset by a decrease in compensation and related personnel expenses of $1.4 million, which are not allocated by program. External expenses include (i) program-specific expenses, which increased by $10.0 million, primarily driven by increases in our ARV-102, vepdegestrant, ARV-393 and other programs of $5.2 million, $5.0 million, $1.4 million and $2.5 million, respectively, offset by decreases in our luxdegalutamide (ARV-766) and bavdegalutamide (ARV-110) programs of $3.6 million and $0.5 million, respectively, and (ii) our non-program specific expenses, which decreased by $2.2 million.
Non-GAAP R&D expenses were $79.3 million for the quarter ended March 31, 2025, as compared with $71.9 million for the quarter ended March 31, 2024, excluding $11.5 million and $12.4 million of non-cash stock-based compensation expense for the quarters ended March 31, 2025 and 2024, respectively. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.
General and Administrative Expenses: GAAP General and administrative (G&A) expenses were $26.6 million for the quarter ended March 31, 2025, as compared with $24.3 million for the quarter ended March 31, 2024. The increase in general and administrative expenses of $2.3 million for the quarter was primarily due an increase in professional fees of $2.4 million, inclusive of an increase in the amortization of costs to obtain a contract of $2.6 million related to changes in total Vepdegestrant (ARV-471) Collaboration Agreement program cost estimates resulting from the removal of two Phase 3 combination trials from the development plan and an increase in costs related to developing our commercial operations of $2.3 million, partially offset by a decrease in personnel and infrastructure related costs of $2.4 million.
Non-GAAP G&A expenses were $23.1 million for the quarter ended March 31, 2025, as compared with $18.0 million for the quarter ended March 31, 2024, excluding $3.5 million and $6.3 million of non-cash stock-based compensation expense for the quarters ended March 31, 2025 and 2024, respectively. A reconciliation of GAAP to non-GAAP financial measures used in this press release can be found at the end of this press release.
Revenue: Revenue was $188.8 million for the quarter ended March 31, 2025 as compared with $25.3 million for the quarter ended March 31, 2024. Revenue for the quarter is related to the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer and the collaboration and license agreement with Pfizer. The increase in revenue of $163.5 million was primarily due to an increase in revenue from the Vepdegestrant (ARV-471) Collaboration Agreement with Pfizer totaling $167.8 million related to changes in total program cost estimates resulting from the removal of the first-line Phase 3 combination trial with Pfizer’s novel investigational CDK4 inhibitor, atirmociclib, and the removal of the second-line Phase 3 combination trial with a CDK4/6 inhibitor from the development plan, offset by a decrease in revenue from the Pfizer Research Collaboration Agreement of $2.7 million due to changes in estimates of the performance period duration under the agreement resulting from updated research timelines and a decrease in revenue from the Bayer Collaboration Agreement of $1.6 million related to the termination of the Bayer Collaboration Agreement in August 2024.
Investor Call & Webcast Details
Arvinas will host a conference call and webcast today, May 1, 2025, at 8:00 a.m. ET to review its first quarter 2025 financial results and discuss recent corporate updates. Participants are invited to listen by going to the Events and Presentation section under the Investors page on the Arvinas website at www.arvinas.com. A replay of the webcast will be available on the Arvinas website following the completion of the event and will be archived for up to 30 days.